Telomerase inhibitors--oligonucleotide phosphoramidates as potential therapeutic agents

Nucleosides Nucleotides Nucleic Acids. 2001 Apr-Jul;20(4-7):401-10. doi: 10.1081/NCN-100002314.

Abstract

We have designed, synthesized, and evaluated using physical, chemical and biochemical assays various oligonucleotide N3'-->P5' phosphoramidates, as potential telomerase inhibitors. Among the prepared compounds were 2'-deoxy, 2'-hydroxy, 2'-methoxy, 2'-ribo-fluoro, and 2'-arabino-fluoro oligonucleotide phosphoramidates, as well as novel N3'-->P5' thio-phosphoramidates. The compounds demonstrated sequence specific and dose dependent activity with IC50 values in the sub-nM to pM concentration range.

MeSH terms

  • Amides / chemical synthesis
  • Amides / chemistry*
  • Amides / pharmacology*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Inhibitory Concentration 50
  • Oligonucleotides / chemical synthesis
  • Oligonucleotides / chemistry*
  • Oligonucleotides / pharmacology*
  • Phosphoric Acids / chemical synthesis
  • Phosphoric Acids / chemistry*
  • Phosphoric Acids / pharmacology*
  • Telomerase / antagonists & inhibitors*

Substances

  • Amides
  • Enzyme Inhibitors
  • Oligonucleotides
  • Phosphoric Acids
  • phosphoramidic acid
  • Telomerase